Discovery opens doors to treating
symptom that can cause the body to attack itself

(Orlando, Florida) – Researchers at the University
of Pennsylvania School of Medicine have identified
a variant of the human gene for tumor necrosis factor-alpha
(TNF-alpha) as the cause for photosensitivity in lupus
patients. This discovery, which was presented today
at the annual scientific meeting of the American College
of Rheumatology, will not only help in treating photosensitivity,
but will also advance research on treating this potentially
damaging symptom and possibly point to one of the genetic
causes of lupus.

Victoria Werth, MD Associate Professor
of Dermatology and Medicine in Penn’s School of
Medicine, working in collaboration with Kathleen
E. Sullivan, MD, PhD, Associate Professor of
Pediatrics, University of Pennsylvania School of Medicine,
and attending physician in The Children's Hospital of
Philadelphia Division of Allergy and Immunology, identified
a variant of the TNF-alpha promoter that showed increased
activity when exposed to sunlight. This discovery is
crucial to understanding photosensitivity and lupus
because TNF-alpha has been shown to stimulate apoptosis,
the process of cellular death. As skin cells die, intracellular
proteins move to the cell’s surfaces where they
stimulate an immune reaction. The immune system makes
new antibodies against these proteins and triggers further
inflammation, causing the body to attack its own internal
organs - just from sunlight.

As part of her research, Werth has studied the effects
of TNF-alpha in cultured cells and patients. She has
found that a large percentage of patients with subacute
cutaneous lupus erythematosus (SCLE), a highly photosensitive
form of lupus, has one or even two copies of the TNF-alpha
variant gene. Thus, when these cells are exposed to
sunlight, the gene becomes overactive, and a large quantity
of TNF-alpha is produced. This causes nearby skin cells
to undergo apoptosis, therefore stimulating the immune
system and triggering flares that could affect internal
organs.

The increased presence of TNF-alpha in lupus patient
cells suggests that additional genetic variants are
associated with increased TNF-alpha production in response
to sunlight. This could mean major advances in treating
lupus patients.

“These results now let us think about different
categories of drugs for treatment of photosensitivity,”
says Werth. While drugs like antimalarials and thalidomide
are already used to inhibit TNF-alpha and treat the
skin manifestations of lupus, these findings allow researchers
to test newer drugs that inhibit TNF-alpha. Also, as
researchers better understand the wavelengths of light
that trigger the disease, they can develop sunscreens
that will hopefully improve the ability to block the
harmful effects of sunlight.

Funding for this research was provided by the Lupus
Research Institute through their Novel Research Program,
which seeks to support highly promising novel approaches
to discover the cause, improve the treatment and cure
lupus.

PENN Medicine is a $2.2 billion enterprise
dedicated to the related missions of medical education,
biomedical research, and high-quality patient care.
PENN Medicine consists of the University of Pennsylvania
School of Medicine (founded in 1765 as the nation's
first medical school) and the University of Pennsylvania
Health System (created in 1993 as the nation's first
integrated academic health system).

Penn's School of Medicine is ranked
#2 in the nation for receipt of NIH research funds;
and ranked #4 in the nation in U.S. News & World Report's
most recent ranking of top research-oriented medical
schools. Supporting 1,400 fulltime faculty and 700 students,
the School of Medicine is recognized worldwide for its
superior education and training of the next generation
of physician-scientists and leaders of academic medicine.

Penn Health System consists of four
hospitals (including its flagship Hospital of the University
of Pennsylvania, consistently rated one of the nation's
"Honor Roll" hospitals by U.S. News & World Report),
a faculty practice plan, a primary-care provider network,
three multispecialty satellite facilities, and home
health care and hospice.

Founded in 1855 as the nation's first pediatric hospital,
The Children's Hospital of Philadelphia is ranked today
as the best pediatric hospital in the nation by U.S.News
& World Report and Child magazine. Through its long-standing
commitment to providing exceptional patient care, training
new generations of pediatric healthcare professionals
and pioneering major research initiatives, Children's
Hospital has fostered many discoveries that have benefited
children worldwide. Its pediatric research program is
among the largest in the country, ranking second in
National Institutes of Health funding. In addition,
its unique family-centered care and public service programs
have brought the 381-bed hospital recognition as a leading
advocate for children and adolescents from before birth
through age 19. Children's Hospital operates the largest
pediatric healthcare system in the U.S. with more than
40 locations in Pennsylvania, New Jersey and Delaware.

The Lupus Research Institute (LRI)
is the national nonprofit organization that supports
only the highest-ranked novel research in lupus. With
a broad-based research agenda, the LRI seeks to change
the course of lupus research to improve treatment, prevent
and cure lupus. Created in collaboration with leading
lupus scientists, the LRI encourages researchers to
search for answers solely in unconventional, innovative
ways. The LRI also supports the development of new clinical
trial methodologies that will accelerate the testing
of promising agents in lupus patients. Currently, the
LRI has awarded more than 7 million in grants, supporting
35 scientists at leading medical institutions around
the country. Specific information on individual research
projects can be obtained at www.lupusresearchinstitute.org.